A transaction between Shire and Takeda is the largest pharma deal of the year.

Takeda has reached a preliminary agreement to buy Adderall drugmaker Shire for $64 billion in the largest pharma deal of the year.

The deal strengthens the Japanese drugmakers' footprint in the US, where Shire has a large presence, and also expands its position in rare diseases like hemophilia.

Takeda, a 300-year-old Japanese drugmaker, has been working to expand its global footprint, most recently with its $5.2 billion purchase of US cancer drug maker Ariad Pharmaceuticals last year. Under CEO Christophe Weber, Takeda is looking overseas for growth amid a shrinking domestic population in Japan and patent expirations for several of its key products.

Takeda first approached Shire in March, and Shire had rejected four of the company's earlier bids. Takeda's pursuit of Shire heated up further last week when Botox-maker Allergan revealed it was weighing an offer for the company. Takeda's shares dropped as much as 9.3% on the announcement of the deal, the biggest fall in five years.

Shire has long been a takeover taket. US drugmaker AbbVie nearly acquired the company in 2014, but the deal collapsed due to changes in US tax law.